Human greater saphenous vein (HSV) remains the most commonly used conduit for coronary and peripheral arterial bypass grafting. HSV is typically harvested from the leg with direct surgical exposure or endoscopic vein harvest. The branches are ligated and the vein is removed and placed on the “back table” prior to implantation. Most surgeons place the HSV in heparinized saline solution at room temperature. The vein is cannulated at the distal end and manually distended (with a syringe) with heparinized saline. This allows for identification and ligation of side branches that have been missed during harvest. This manual distension leads to injury to the vein. The veins are also marked with a surgical skin marker to optimize orientation during implantation.
Of the more than 1 million coronary bypass procedures that are undertaken each year worldwide, 10-15% of coronary vein grafts undergo early thrombotic occlusion; an additional 10-15% occlude in the next 1-5 years due to intimal hyperplasia, with a further 30-40% occluding in the subsequent 5-7 years because of progressive atherosclerosis superimposed on intimal hyperplasia. Less than half of vein grafts remain patent after 12 years (Motwani & Topol, 1998). Vein graft occlusion leads to myocardial infarction, limb loss, and death.
The leading cause of failure of arterial bypass grafts is intimal hyperplasia (Clowes & Reidy, 1991). Despite the many recent technological advances in vascular interventions, intimal hyperplasia remains an expensive, morbid, and unsolved problem. Intimal hyperplasia is mediated by a sequence of events that include vascular smooth muscle proliferation, migration, phenotypic modulation, and extracellular matrix production (Allaire & Clowes, 1997; Mosse et al., 1985). This process leads to pathologic narrowing of the vessel lumen, graft stenoses, and ultimately graft failure (LoGerfo et al., 1983).
A number of drugs that have been tested for their capacity to inhibit intimal hyperplasia have failed in clinical trials. Antithrombotic and antiplatelet agents such as warfarin, clopidogrel, and aspirin, have little or no effect on intimal hyperplasia (Kent & Liu, 2004). Drug eluting stents have been shown to be effective in preventing restenosis after coronary angioplasty; however, no therapeutic has been approved for autologous conduits. Two large clinical trials for the prevention of coronary and peripheral vascular vein graft failure using an E2F decoy (a short sequence of DNA that binds to transcription factors, sequestering these proteins) to prevent smooth muscle proliferation failed in their primary endpoint. Data from these large clinical trials suggests that simply limiting the proliferation response is not adequate to prevent intimal hyperplasia (Mann et al., 1999; Alexander et al., 2005). Therefore mechanisms other than proliferation need to be targeted for successful prevention of vein graft failure.
Injury to the vein graft during harvest leads to vasospasm and intimal hyperplasia, which cause the grafts to occlude. Thus, it would be of great benefit to identify new surgical methods and therapeutics to prevent injury to the graft during harvest and subsequent intimal hyperplasia.